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Abstract

MicroRNAs (miRs) have emerged recently as important regulators of gene expression
in the cell. Frequently dysregulated in cancer, miRs have shed new light on molecular
mechanisms of oncogenesis, and have generated substantial interest as biomarkers,
and novel therapeutic agents and targets. Recently, a number of studies have examined
miR biology in Ewing sarcoma. Findings indicate that alterations in miR expression
in Ewing Sarcoma are widespread, involve both EWS/Ets oncogenic fusion-dependent and
independent mechanisms, and contribute to malignant phenotypes. miRs with prognostic
potential have been identified, and several preclinical studies suggest that miR manipulation
could be therapeutically useful in this aggressive disease. These and future studies
of miR biology stand to expand our understanding of Ewing sarcoma pathogenesis, and
may identify new biomarkers and treatment options.

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MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

Small RNAs of 20-30 nucleotides can target both chromatin and transcripts, and thereby keep both the genome and the transcriptome under extensive surveillance. Recent progress in high-throughput sequencing has uncovered an astounding landscape of small RNAs in eukaryotic cells. Various small RNAs of distinctive characteristics have been found and can be classified into three classes based on their biogenesis mechanism and the type of Argonaute protein that they are associated with: microRNAs (miRNAs), endogenous small interfering RNAs (endo-siRNAs or esiRNAs) and Piwi-interacting RNAs (piRNAs). This Review summarizes our current knowledge of how these intriguing molecules are generated in animal cells.

MicroRNAs are important regulators of gene expression that control both physiological and pathological processes such as development and cancer. Although their mode of action has attracted great attention, the principles governing their expression and activity are only beginning to emerge. Recent studies have introduced a paradigm shift in our understanding of the microRNA biogenesis pathway, which was previously believed to be universal to all microRNAs. Maturation steps specific to individual microRNAs have been uncovered, and these offer a plethora of regulatory options after transcription with multiple proteins affecting microRNA processing efficiency. Here we review the recent advances in knowledge of the microRNA biosynthesis pathways and discuss their impact on post-transcriptional microRNA regulation during tumour development.

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